Chronic parasitic co-infection has been postulated to increase the rate of progression to AIDS in sub- Saharan Africa . Uganda is one such country in which HIV has spread rapidly and where a high seroprevalence of schistosomiasis has been documented. It has been proposed that chronic Schistosoma mansoni (S. mansoni) infection promotes an immune profile that facilitates HIV replication and impairs the host's antiviral immune response. The impact of S. mansoni co-infection in HIV pathogenesis is not yet fully understood. Schistosomiasis has previously been associated with a more severe clinical course in chronic viral infection and with impaired viral-specific T cell dysfunction. However, no study to date has reported changes in the HIV-specific immune responses in co-infected individuals. We hypothesize that the S. mansoni co-infection alters the determinants of clinical outcome and antiviral cellular immunity in HIV disease. This study proposes to examine potential factors implicated in the pathogenesis of S. mansoni coinfection in Uganda. This project will optimize and build on the established research and laboratory infrastructure of the Joint Clinical Research Centre (JCRC) with the experience and talents of the Ugandan scientific community and the collaboration and assistance of external experts. The proposed aims build on existing reports as well as preliminary data generated at the JCRC and the US laboratories. Specifically, our aims are:1)To conduct a longitudinal study in a clinic-based cohort of HIV seropositive Ugandan volunteers in Kampala and evaluate the effect of S. mansoni co-infection on HIV disease progression. 2) To evaluate whether S. mansoni infection affects the host's ability to generate HIV antiviral immune response. 3)To explore the hypothesis that S. mansoni infection dysregulates cellular immune responses by enhancing the activity of IL-10-producing T cells. S. mansoni co-infection will therefore be examined in the context of being an experimental immune modulator.